Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis

Arthritis Rheum. 2003 Jul;48(7):1858-72. doi: 10.1002/art.11171.


Objective: To evaluate the possible role of activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin (Lptn) in the pathogenesis of rheumatoid arthritis (RA).

Methods: ATAC/Lptn levels in serum and synovial fluid samples were measured by sandwich enzyme-linked immunosorbent assay. Expression of messenger RNA for ATAC/Lptn in synovial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) and by in situ hybridization, and was quantitated by real-time PCR. The phenotype of peripheral blood mononuclear cells (PBMCs) expressing ATAC/Lptn was analyzed by intracellular cytokine staining and flow cytometry.

Results: Levels of ATAC/Lptn were similar in sera and synovial fluids from RA patients (n = 20) and osteoarthritis controls (n = 15). In phorbol myristate acetate/ionomycin-stimulated PBMCs, ATAC/Lptn expression was detected in CD8+ T cells and in a significantly increased proportion of CD4+,CD28- T cells from RA patients as compared with healthy controls. In synovial tissues, ATAC/Lptn was predominantly localized in CD3+ T cells in the sublining layer. Lymphocytes, synovial macrophages, and, unexpectedly, fibroblast-like synoviocytes (FLS) were identified as major target cells for ATAC/Lptn in RA synovium, as determined by analysis of the ATAC/Lptn receptor XCR1. In vitro, ATAC/Lptn stimulation of FLS resulted in a marked down-regulation of matrix metalloproteinase 2 production.

Conclusion: These data indicate that in RA synovium, ATAC/Lptn is mainly produced by T cells. Considering its function as a lymphocyte-specific chemoattractant, ATAC/Lptn might be a key modulator for T cell trafficking in the pathogenesis of RA. In addition, functional studies suggest that ATAC/Lptn may exert additional immunomodulatory effects in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Chemokines, C*
  • Female
  • Gene Expression / immunology
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Lymphokines / genetics
  • Lymphokines / immunology*
  • Lymphokines / pharmacology
  • Male
  • Middle Aged
  • Osteoarthritis / immunology
  • Phenotype
  • RNA, Messenger / analysis
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / immunology*
  • Sialoglycoproteins / pharmacology
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism


  • Chemokines, C
  • Lymphokines
  • RNA, Messenger
  • Sialoglycoproteins
  • XCL1 protein, human
  • lymphotactin